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A recent release from the U.S. Food and Drug Administration (FDA) has highlighted that caution is needed with the use of testosterone replacement treatments for men.

US FDA statement on Testosterone Replacement

Their advice suggests that replacement should only be used for men who have low testosterone levels caused by certain medical conditions such a primary hypogonadism (examples are failure of the testes to produce testosterone due to chemotherapy, genetic conditions, damage from infection), or disorders of the brain or pituitary gland that result in decreased testosterone.

Increasingly, testosterone replacement is being used to treat symptoms in men who have low testosterone for no other apparent reason other than due to ageing. The USFDFA state that the benefits and safety of testosterone replacement have not been established for this use.

Some studies suggest there may be an increased risk of cardiovascular problems (heart attack and stroke) with testosterone replacement, although not all studies have demonstrated this.

It is very important that you talk with your doctor about these risks, and the indications for starting testosterone replacement.

Our latest Guest Blog is by Dr Michael Wong, Director of the Singapore Urology, Fertility and Gynaecology Centre. He is a US Fellowship Trained Urologist, and previous President of the Singapore Urology Association. Michael gives an up to date and comprehensive account of Infective Complications in the Surgical Management of Urinary Stones.

Infective Complications in the Surgical Management of Urinary Stones

Introduction

Despite the significant advancements in the surgical management of urinary stones, morbidity and even mortality are still being reported. Krambeck reported in the Journal of Urology in 2013 that deaths still occur after surgery, particularly in the elderly population as their immunity is lower and there could be delay in diagnosis due to lack of classical symptoms. The importance of appropriate antibiotic prophylaxis and assessment of risk factors prior to treatment cannot be underestimated.

Infective Issues with Percutaneous Nephrolithotomy (PCNL)

PCNL is most appropriate for large renal stones. One of the feared complications of PCNL is urosepsis. A common composition for staghorn stones is struvite,5 which results from the presence of urea-splitting organisms, and non-struvite stones may also harbor bacteria. There is therefore an increased risk for sepsis during the procedure. Further, PCNL utilizes large volumes of irrigation relative to ureteroscopy, which may increase the risk of sepsis.

The practice of prophylaxis for PCNL is not for debate. David Tolley reported that the rate of UTI reduces 3 fold when using prophylaxis for PCNL. Recently, the CROES group reported a series of 162 patients from multiple institutions who underwent PCNL without pre-operative antibiotics and matched them to patients who did receive antibiotics6 All patients had negative pre-operative urine cultures and matching was based on infectious risk factors such as diabetes, nephrostomy tubes and staghorn stones. They found that antibiotic prophylaxis led to fewer fevers (2.5% vs. 7.4%) and other complications (1.9% vs. 22%) and higher stone free rate (86.3% vs. 74%). The explanation for this finding may be that stones themselves may harbor bacteria that may not manifest in a voided urine culture.

Techniques to culture stones were described over 40 years ago. In a study examining infection rates in patients undergoing PCNL, 35% of patients had positive stone cultures, compared with 21% of upper tract and 11% of bladder urine cultures. Stone manipulation and lithotripsy can result in the release of bacteria and contamination of urine with possible systemic transudation resulting in sepsis or systemic inflammatory response syndrome (SIRS). Stone cultures have been shown to be a better predictor of sepsis and SIRS than voided cultures. Mariappan showed a positive stone culture to have over 80% sensitivity and a positive predictive value of 70% in predicting SIRS.7 Overall, positive stone cultures increased the risk of SIRS 4-fold. Along with bacteria, stones contain endotoxins that can potentially result in a systemic immune response clinically similar to sepsis.

The greatest limitation of stone cultures is that they are only available after a procedure with some days to allow bacteria culture and so cannot influence immediate peri-operative treatment. The utility of obtaining stone cultures in clinical practice is to guide antibiotic choice in the event of sepsis following ureteroscopy or PCNL rather than predicting it. Having said this, it is reassuring to routinely collect stone cultures intraoperatively from patients undergoing PCNL.

Understanding the Risk factors for Urosepsis during PCNL

Many groups have reviewed their experience with PCNL in an attempt to identify risk factors for post-operative fever, sepsis or SIRS. A positive pre-operative urine culture was associated with increased infectious risk (OR 2.2 -16.7), as were positive pelvic urine (OR 10.2 – 24.1) and stone cultures (4.88 – 25.6). Other factors such as female sex, hydroureteronephrosis, pre-operative nephrostomy tube, large or complex stone burden, and diabetes have all been associated with an increased risk of post-operative fever or sepsis.

Korets and colleagues showed that an increased number of access tracts increased the risk of SIRS (HR 4.8) when controlling for patient sex, stone culture and composition, while several other groups have found increased operative time to be a risk factor for fever. Dogan also showed volume of irrigation fluid required was a significant predictor. These three factors are likely all surrogates for stone size and complexity, resulting in a prolonged procedure.

Infective Issues with Ureteroscopy

A 2003 RCT by Knopf et al. that included 113 patients found a single prophylactic oral dose of fluoroquinolone prior to ureteroscopy reduced the incidence of post-operative bacteriuria (1.8% vs. 12.5%, p=0.02). There were, however, no incidences of symptomatic UTI. This study guided the AUA Best Practice Policy in recommending antibiotic prophylaxis prior to ureteroscopy for the management of stone disease.3 The guideline committee states that the potential risk of bacteriuria is 30% and UTI ranges from 4% - 25% without prophylaxis. There is no difference in efficacy between oral fluoroquinolone and intravenous cefazolin.

A Korean group reviewed their experience of infectious complications following ureteroscopy and identified several risk factors.4 They noted an overall UTI rate of 3.8%. Furthermore, they found hydronephrosis, bacteriuria, and an indwelling ureteral stent or nephrostomy tube was associated with an increased risk of post-procedural fever. Administration of antibiotics after the procedure was not as effective as pre-procedural prophylaxis.

Eswara and colleagues retrospectively reviewed their experience with stone cultures in patients undergoing ureteroscopy (n=274) or PCNL (n=54). They found that while pre-operative urine cultures were only positive at some point in 7% of patients, stone cultures were positive in 29%. Their overall sepsis rate was about 3-4% for all patents. In patients with positive stone cultures, the sepsis rate was significantly higher at 8% compared to only 1% in those who had negative stone cultures. Ultimately, urine cultures had a sensitivity of 11% versus 64% in stone cultures and there was a concordance of 64% between the stone culture pathogen and the one causes sepsis compared to only 9% of pre-operative urine cultures. Despite the correlation of stone cultures and post-operative infection, their utilization in guiding clinical practice is limited in that it takes several days following the removal of the stone for cultures to results. They are most helpful following the development of UTI to help guide antibiotic choice.

Unfortunately we do not have a study showing the use of ureteric stent post URS reduces UTI as upper tract decompression using a stent would also play a part in reducing UTI.

Infective Issues in Extra-Corporeal Shock Wave Lithotripsy (ESWL)

In general, the incidence of urinary tract infection occurring after uncomplicated ESWL is less than 1%, rising to 2.7% for staghorn calculi. This risk of sepsis increases in the presence of bacteriuria prior to ESWL especially if there is distal obstruction.

Until recently, the practice of giving prophylactic antibiotics was controversial in patients undergoing ESWL with negative urine cultures. It has been reported that bacteriuria can develop in 5-6% of patients undergoing ESWL even in the presence of sterile urine prior to the procedure and the risk of clinical UTI can be seen in 2-3% subsequently.

The European Association of Urology guidelines on urological infections (updated in 2010) do not recommend prophylactic antibiotics in ESWL unless there are risk factors like ureteral stents, urinary catheters, nephrostomy tubes or infective stones1.
More recently, in a meta-analysis reported in the Journal of Urology in 2012 covering 9 randomized trials of 1364 patients undergoing ESWL for urinary stones with sterile urine cultures2, Lu et al reported no significant differences between the prophylactic group and the control group in terms of symptoms, rate of fever, rate of positive urine culture and the incidence of urinary tract infection. They suggested that antibiotic prophylaxis is not necessary for ESWL in low risk patients.

The American Urological Association guidelines3 were recently updated in Jan 2014 and currently do not recommend antibiotic prophylaxis for patients undergoing ESWL with negative urine culture. In the light of more recent publications, prophylactic antibiotics are recommended only in high risk stone groups with infective stones, recent instrumentation, nephrostomy tubes, positive urine cultures and a history of recent UTI or sepsis. In addition, special considerations should also be given to high risk patient groups which the AUA defines as advanced age, anatomical anomalies of the urinary tract, poor nutritional status, chronic smokers, chronic steroid users, immunodeficiency, externalized catheters and prolong hospitalisation.

In general, ESWL should only be performed if the urine is sterile and when there is no distal obstruction to minimise infective complication. Currently, prophylactic antibiotics should be considered only in high risk patients.

Conclusion

The current guidelines and practice patterns pertaining to stone surgery have evolved based on emerging clinical data. These recommendations in conjunction with patients’ individual risk factors and culture data should help guide ongoing practice patterns.

This is Professor David Gillatt's second blog on the site. Here, he talks about the indications for salvage radical prostatectomy for prostate cancer, its indications and some of the difficulties encountered in this rarely performed surgery.

David, can you explain what salvage prostate cancer surgery is?

As we all recognise, unfortunately, in a minority of cases treated for prostate cancer the disease will recur despite that treatment. When a man has had radiation treatment for what appears to be prostate cancer confined to the prostate or its immediate surrounds, some will in time show evidence of the cancer reappearing and starting to progress. This will also happen in the less common situation of the cancer being treated with other local therapies such as cryotherapy, high intensity focussed ultrasound or brachytherapy. The disease comes back either because the treatment failed to control the cancer within the prostate or there was disease already microscopically beyond the gland which will eventually lead to spread. If the recurrent cancer is still within the prostate and detected early it may still be at a curable stage. This is the point at which we can consider salvaging the situation by surgically removing the prostate and the recurrent cancer therein.

If a patient has failed another treatment, what are the factors determining suitability for salvage surgery?

Salvage surgery is a local therapy and as such it will only remove or cure a cancer if still within the prostate. Therefore a judgement needs to be made when recurrence has occurred as to whether the disease has a high likelihood of being localised or are there features that suggest the probability of at least micrometastatic cancer.

Recurrence usually is suspected because the serum PSA begins to rise after falling to low levels after initial therapy. A variety of definitions of recurrent cancer after radiation have been used; the ASCO (American Society of Clinical Oncology) defined failure as the lowest PSA (nadir) after therapy plus 2 units of PSA is the most commonly accepted. This is applied by many to all forms of local therapy, apart from surgery, for prostate cancer.

If recurrence is suspected in my view a thorough search for obvious metastatic disease, including CT chest/abdomen/pelvis, isotope bone scan and occasionally PET scanning is mandatory. MRI and occasionally Choline PET scanning may define local recurrence. Antibody labelled isotope scanning (Prostascint for example) has been evaluated but is not in routine usage. The presence of obvious metastatic disease or locally advanced T3/4 N+ cancer will usually be a contraindication to salvage surgery.

A biopsy is again essential to define local recurrence and may be done once imaging has confirmed that the disease has not obviously spread. Confirmation of local recurrence in the absence of spread may be an indication for salvage surgery.

One further factor that must be taken into account is the behaviour of the patient’s PSA. The PSA velocity or doubling time give an indication of how much risk of progression the cancer poses to the individual over their lifetime. A rapid doubling of PSA, less than every 3 months, confers a high risk of the cancer spreading and resulting in early death. A slow doubling, more than one to two years, indicates a risk as low as perhaps 10 % of the cancer progressing over the next 10 years or more. As with many stages of prostate cancer there is a balance between needing to treat successfully those at high risk of causing damage and death and not over treating those with a very low risk of progress.

In summary a man with prostate cancer previously treated with radiation with PSA evidence of recurrence requires specialist assessment. A variety of factors including the stage of the cancer, the PSA behaviour and the life expectancy of the individual need to be considered before embarking on salvage surgery.

Obviously, this is difficult surgery. Can you outline the side effects of the operation?

This type of surgery, whether performed by the open route, laparoscopically or with robotic assistance is undoubtedly far more difficult and complex than primary radical prostatectomy. The effect of radiation, or indeed HIFU or cryotherapy, results in marked tissue reaction around the prostate. The prostate lies very close to many important organs and the effect of radiation is to make dissection of these areas more difficult and the risk of injury to other structures much more likely. Even when injury does not occur the healing of tissues is less certain following radiation. Collateral radiation effects on the distal urethral sphincter, neurovascular bundles and bladder neck may also make functional recovery slower and long term side effects more likely.

The rectum lies close to the posterior prostate and will often be quite stuck after radiation. Surgical dissection needs to be very careful in this region as injury to the rectum increases the risk of infection, fistula (a connection between the bowel and bladder resulting in urine leaking into the rectum) and the need for a colostomy. While this complication is still uncommon it is more so than after radical prostatectomy with no prior radiation.
Incontinence is common in the short term after radical prostatectomy, resolving relatively rapidly in most. After salvage radical prostatectomy, the risk of incontinence is much higher, the time to recovery longer and long-term problems more common. At least 30-40% of men may experience long-term continence issues, some requiring correction, after salvage prostatectomy.

Sexual dysfunction, mainly erectile problems, are very common after salvage prostatectomy as the bundles may well have been compromised by the radiation before embarking upon a difficult salvage procedure.
Because of fibrosis (scarring) around the bladder neck subsequent contractures requiring dilatation are common and in some will further increase the chance of long-term continence problems.

Can the operation be performed by laparoscopic or robotic methods?

The answer is yes; salvage prostatectomy can be performed by any of the recognised methods of radical prostatectomy. Is there evidence in favour of one procedure over another? – There is no evidence as there have been no trials comparing the techniques in this situation. As with many difficult procedures the likelihood of a successful outcome will in large part depend upon the experience of the surgical team dealing with the operation.

You are a high volume prostate cancer surgeon, but this is quite a rare operation. How many of these salvage prostatectomy operations do you perform per year?

Salvage prostatectomy is an uncommon operation even in very large busy prostate cancer centres. Even in US centres where 3-6,000 or more robotic prostatectomies have been performed the number of salvage cases is often far less than 100. The Bristol experience has been around 2000 open radical prostatectomies of which around 65 were salvage and over 1000 robotic cases, in 21 cases these were salvage cases. Our outcomes including functional recovery have been very good. However as these numbers suggest, most specialist units are very selective about to whom they offer salvage radical prostatectomy.

One interesting question is should we be considering more men for salvage RP? Undoubtedly the answer is yes. The perceived morbidity of all salvage treatments and the uncertainty as to which men most benefit from this approach has led many oncologists to take an observational approach. It is the urological cancer surgeons’ role to convince our Medical and Radiation oncological colleagues that appropriate salvage surgery can deliver a high chance of cure to men with locally recurrent prostate cancer at risk of progression in their lifetime with acceptable functional outcomes. It is my belief that minimally invasive surgery, in particular robotically assisted LP, offers the opportunity for the experienced prostate cancer surgeon to deliver salvage surgery safely, effectively and with rapid recovery times.

This week’s Guest Post is by Dr Addie Wootten, a Clinical Psychologist with Australian Prostate Cancer Research and The Department of Urology, Royal Melbourne Hospital. She talks about the psychological impact of prostate cancer on men, and what can be done to help.

The Psychological impact of prostate cancer

A prostate cancer diagnosis, like all diagnoses of cancer, can have a significant impact on psychological and emotional wellbeing. Many men speak about the shock, fear, uncertainty and anxiety they experienced when told they had prostate cancer. Many men also speak about the diagnosis as feeling like it ‘came out of the blue’ as many men are diagnosed with localised prostate cancer without any symptoms of warning. Unfortunately many men experience periods of depression or anxiety following a diagnosis of prostate cancer and emerging data indicates that men with prostate cancer have a higher risk of suicide than other men their age. This indicates the significant emotional impact that prostate cancer can have on some men.

Prostate cancer can have a very personal impact

While the initial shock of a cancer diagnosis can take its toll it is often the side-effects of prostate cancer treatment that men find the most challenging. Unfortunately all treatment options come with their share of side effects, but different treatments will have different side-effects. All treatments will have an impact on sexual and erectile functioning including changes or loss of ejaculation, changes in orgasm sensation, loss of penile length and changes to penile sensitivity but at different levels and rates depending on the treatment type. These side effects can have a significant personal impact for many men as well as a direct impact on their intimate relationships.

For many men the loss of sexual functioning can be even more difficult because of remaining normal sexual desire and this can compound the significant loss and associated impact on masculinity and self-esteem. Urinary incontinence can also have a very personal impact in terms of self-esteem, ability to maintain social connections and the experience of anxiety. Self-esteem, masculine identity and self-confidence can be significantly impacted on by the experience of prostate cancer and treatment side effects.

Managing these challenges

We know from the research literature that one of the biggest predictors of psychological distress post prostate cancer treatment is unrealistic expectations pre-treatment. That is, men who are not fully informed and counseled, pre-treatment, about the impact of treatment on their physical functioning (particularly the sexual impact) will experience much higher levels of distress post-treatment. While this isn’t rocket science the delivery of adequate information and support prior to treatment in preparation for these side-effects surprisingly doesn’t occur all the time. Many men report feeling ill-informed, and unsupported, in navigating life with these side effects.

So what role does a psychologist play in prostate cancer?

As a clinical psychologist I have the privilege of hearing the very personal experiences of men affected by prostate cancer and their partner or spouse. My role in working with these men and couples is to explore the personal impact of their experience and help them weave a new way of living, whether that be a new way of being intimate, a new outlook on life or a new level of emotional awareness.

A large part of my role is to help men and their partners explore what it might mean to experience the side effects of treatment before they have treatment. I try and speak with both members of the couple before treatment to help them plan and prepare for life after treatment and to ensure they fully understand how this might impact on them personally and as a couple. These issues are also the focus of much of my work after treatment.

A clinical psychologist will also be looking out for symptoms of anxiety and depression and other mental health concerns and will provide psychological counseling that focuses on reducing these symptoms and improving emotional wellbeing.

How to access a psychologist

Seeing a psychologist is not routine in most practices but there are many psychologists available in Australia. Ask your specialist or nurse for a referral. If they don’t know of anyone in your local area, check with your GP. If you still can’t find the right person there is an excellent listing of psychologists on the Australian Psychological Society website

To get a rebate back through Medicare you will need a referral from your GP with a mental health care plan. This care plan entitles you to up to 10 rebateable sessions per year.

New online support

I have been working to develop easily accessible psychological support for men following treatment for prostate cancer and I am currently running a study evaluating the benefits of an online support program called My Road Ahead. I am currently looking for men who have had treatment for localised prostate cancer to participate. To learn more go to myroadahead

Another new online program I have been working on is called PROSTMATE. This is an online prostate cancer portal that provides tailored information, a place to record treatments, appointments and track progress and also offers web-based consultations with prostate cancer nurses and psychologists. Follow this link to learn more about PROSTMATE

Acknowledgement

I would like to acknowledge the men and their partners who I have worked with over the years who have helped me understand the personal loss and the impact of prostate cancer; I would particularly like to acknowledge James Waller in sharing his insights.

This week’s Guest Post is by Denby Steele, an Adelaide Urologist, an expert in the management of complex kidney stone disease and pioneer of supine PCNL in Australia

"Marberger, Clayman and Whickam, in different parts of the world, were instrumental with the development of percutaneous stone surgery in the late 1970’s and early 1980’s, and for many years this has been performed in the prone position. Extracorporeal shock lithotripsy in the early 1990’s and flexible ureteroscopic laser lithotripsy in the later 1990’s have provided less invasive alternatives for upper tract stone surgery but percutaneous surgery still offers an excellent minimally invasive option, particularly for larger stones.

"Traditionally, percutaneous stone surgery has been performed in the prone position but since the first description of this in the supine position by Valdivia et al in the Journal of Urology in 1998, there have been pockets of interest and increasing expertise in surgery in this position.

"My series of 322 cases published in the Journal of Endourology in 2007 is still the second largest published series, but there are increasing reports from around the world and numerous reviewers and commentators have highlighted the advantages of surgery in this position. Randomised trials have proven the safety, efficacy and time saving.

"The supine position was presumably neglected because of fear of colonic injury, but it has been shown radiologically that the colon floats further away from the kidney in the supine position, exposing a greater area for safe percutaneous puncture. With the patient tilted over a 3 litre bag under the flank it is possible to puncture even more posteriorly than some prior prone punctures. There have been no reports of colonic perforation in the supine position in the literature.

"There has been debate about which position is best, but this will depend on the sex of the patient, body habitus, whether concomitant rigid lower tract instrumentation is required, stone burden and position of the colon relative to the kidney. I recommend a 3 litre (1 litre in small patients) saline bag under the ipsilateral flank, a pillow under the ipsilateral leg for males, and lithotomy position for females or males requiring a rigid cystoscopy or ureteroscopy. The ipsilateral arm is always brought across the chest. The flank and perineum are prepared and draped together for a single stage procedure starting with flexible cystoscopy and ureteric catheterisation over a glide wire. The image intensifier is angled back 5 – 10 degrees to allow for the patient tilt. Kidney puncture, tract dilatation and stone surgery are then performed in the standard fashion. I tend to leave a ureteric stent afterwards and drain the bladder but do not leave a nephrostomy tube.

"The supine position is very attractive to nursing staff, anaesthetists and surgeons, and offers the following advantages:

Reduced manual handling with no position change

No dangerous prone position

No patient shoulder strain

Single set up and draping

Easy concomitant rigid cystoscopy and ureteroscopy

Comfortable surgery in the sitting position

Reduced radiation to the surgeon as hands not under the image intensifier

Increased safety as it is easy to pass a wire through the puncture and out the urethra

Stone fragments will spontaneously exit the obliquely placed sheath

Reduced operating theatre time

"I have performed percutaneous surgery in the supine position in all 680 cases since 1999 and regularly lecture and run workshops in Australia and overseas to promote and teach this simple and improved technique."

Denby Steele is a Urologist in private practice in North Adelaide South Australia, a Senior Visiting Urologist at the Royal Adelaide Hospital, the inaugural Chairman of the Endourology Special Advisory Group of the Urological Society of Australian and New Zealand, the immediate past Chairman of the SA & NT branch of the Urological Society of Australian and New Zealand and an examiner in Urology for the Royal Australian College of Surgeons.

David Nicol is a Consultant Urological Surgeon at the Royal Marsden Hospital in London where he is also Chief of Surgery. His clinical work deals with complex kidney and testis cancer including surgery in patients with advanced and metastatic disease. Here, he explains the use of cytoreductive nephrectomy in metastatic kidney cancer.

David, can you explain what is meant by cytoreductive nephrectomy?

Cytoreductive nephrectomy refers to the removal of the primary kidney tumour in patients who have metastatic disease. Historically it had been noted that occasional patients experienced spontaneous regression of metastatic disease when this was performed. This however only occurred in a very small number of cases and general opinion was that cytoreductive nephrectomy as the overwhelming majority died within 12-18 months from metastatic disease. In the late 1980’s and early 1990’s, drugs which stimulated the immune system(immunotherapy) had an effect on metastatic kidney cancer.

Small trials with 2 agents interferon-alpha (IFN-a) and interleukin-2 (IL-2) showed response rates better than what had been observed with conventional cytotoxic chemotherapy. Analysis of these studies suggested that patients who had a nephrectomy performed prior to treatment resulted in a better response to both INF-a and IL-2. The basis for this was uncertain with possibilities including a selection bias with only fitter patients, who would otherwise expect to live longer, having nephrectomy. Alternatively it was also proposed that cytoreductive nephrectomy may exert some biological effect improving the effectiveness of immunotherapy and thus overall survival.

Which patients with metastatic kidney cancer are suitable for cytoreductive nephrectomy?

Cytoreductive nephrectomy is really only an appropriate option for patients who are otherwise well. Patients whose performance status is impaired are at high risk of complications from major surgery and also generally have poor survival that is not improved with cytoreductive nephrectomy. Therefore patients who have noted significant weight loss, are anemic or who feel tired and generally unwell are not considered candidates for cytoreductive nephrectomy. Some patients may present with significant symptoms including pain and bleeding for which nephrectomy is recommended. This is regarded as a palliative intervention to control symptoms rather than a cytoreductive nephrectomy which is performed with the expectation that it may improve survival.

Can you outline the evidence that cytoreductive nephrectomy can be beneficial in some patients?

There are 2 trials – one performed in Europe and another in the United States that have demonstrated a survival benefit with cytoreductive nephrectomy in patients who are subsequently treated with IFN-a. These were both randomised controlled trials - in which patients, who all received IFN-a were randomly allocated to either cytoreductive nephrectomy or no surgery. Comparing the 2 groups which were of equal size revealed that patients undergoing cytoreductive nephrectomy had a median survival of 14 months compared to 8 months without. These studies also reinforced the lack of benefit in patients with poor performance status.

This is obviously difficult surgery. Are complication rates much higher compared to other forms of kidney cancer surgery?

Patients with metastatic kidney cancer usually have quite large primary tumours with a rich blood supply being a common feature. Both of these factors can make surgery very difficult and associated with a higher risk of complications, particularly major bleeding, compared to other forms of kidney cancer surgery. Most patients with kidney cancer have relatively small tumours and are able to have surgery performed either laparoscopically or robotically with low risk of complications. In contrast cytoreductive nephrectomy, in almost all cases, requires major open surgery as minimally invasive procedures are usually neither feasible nor safe. Patients with metastatic cancer are also generally at higher risk of complications with major surgery. Deep venous thrombosis and pulmonary embolism are 2 specific examples of this.

A relatively new treatment for metastatic kidney cancer is a class of drugs called tyrosine kinase inhibitors (TKIs). Is there any evidence that cytoreductive nephrectomy followed with TKIs is beneficial for patient outcomes and survival?

The treatment of metastatic kidney cancer has rapidly changed and now IFN-a and IL-2 are rarely used. Both agents have been largely replaced by a new group of drugs – termed targeted therapies due to their effect as tyrosine kinase inhibitors (TKIs). These drugs have a completely different mechanism of action – rather than stimulating the immune system they target tumour blood vessels. Essentially they reduce the blood flow to tumours.

At this point in time it is unknown whether or not cytoreductive nephrectomy improves the outcome in patients treated with TKI’s. It is important to note that the previous studies on cytoreductive nephrectomy only addressed the question as to whether or not this improved survival when patients were treated with IFN-2. Accepting the lack of clear evidence at this time it can still be considered in some patients. For example a patient who is otherwise well presenting with a kidney cancer and small volume metastatic disease I would suggest a cytoreductive nephrectomy as their initial management. The patient would then be observed, avoiding drug treatment until they show clear evidence of substantial progression of their metastatic disease. The rationale behind this is that TKI’s can have significant toxicity and also that resistance to treatment inevitably develops. By removing the kidney and delaying drug therapy the patient avoids toxicity of treatment and also emergence of resistance at a time when their metastatic disease may be stable or only slowly progressing(ie reserving it for maximum effect when it is really needed).

A different approach to cytoreductive nephrectomy would be considered in the patient with high volume or symptomatic metastatic disease. In this scenario I would not recommend cytoreductive nephrectomy as an initial step. Rather the patient should consider commencing a TKI from the outset. Surgery could delay therapy during which time his disease may progress with an overall deterioration in his condition such that he is never suitable for a TKI (as again these drugs only appear of benefit in patients with good performance status).